Technical Field
The present disclosure relates to the field of coated titanium implants, which have been widely used as grafting materials. The present disclosure relates in particular to a method for coating a surface of a titanium implant with low crystalline hydroxyapatite having bioabsorbability, and to an implant coated by such a method.
Description of the Related Art
In recent years, hydroxyapatite has been widely used as an artificial biomaterial capable of replacing hard tissues such as bones or teeth. Hydroxyapatite is a material that is chemically and crystallographically identical to mineral components which constitute bones and teeth in the human body. When transplanted into the human body, hydroxyapatite exhibits high biocompatibility with the surrounding cells and rapidly forms a chemical bond directly with bones at the junction region. A pure hydroxyapatite crystal composed of calcium ions, phosphate ions, and hydroxyl ions is a stoichiometric crystal having a rod-like structure and has a high crystallinity. On the other hand, a biocrystal isolated from bones or calcified cartilage is a nonstoichiometric hydroxyapatite which has a low crystallinity (see J. C. Elliott, In Structure and Chemistry of the Apatites and Other Calcium Orthophosphates, Studies in Inorganic Chemistry 18, Amsterdam: Elsevier, pp 111-190 (1994)).
Titanium has been widely used as an implant material due to having physical properties similar to those of human bones and excellent mechanical strength. Further, titanium has been extensively used as a biological metal since it does not cause inflammatory responses or other immune responses in vivo. In order to impart bioactivity to titanium for industrial applications, titanium is subjected to a variety of surface modifications such as blasting, acid etching, and the like (see numerous patent documents including Korean Patent Application No. 98-23075). However, titanium disadvantageously exhibits poor biocompatibility as compared to ceramic materials such as hydroxyapatite, and undergoes dissolution of metal ions upon long term residence thereof in the human body, which consequently results in the formation of in vivo inorganic substances.
For these reasons, there have recently been developed a variety of methods for obtaining a biomaterial having both excellent mechanical strength and biocompatibility for use in replacement of biological hard tissues by coating titanium with a hydroxyapatite thin film. Conventional representative methods of coating a ceramic, thereby imparting bioactivity to a surface of titanium, may include plasma spraying, sputtering, ion implantation, ion beam deposition, and the like. In order to form a crystalline film in which crystallographical properties of hydroxyapatite are similar to those of biocrystals, various approaches using a calcium phosphate solution or a simulated body fluid have been undertaken.
Plasma spraying which has been most commonly used among the above-mentioned methods has shortcomings such as non-uniformity of a coating layer due to instantaneous exposure to a high temperature of 10,000° C. or higher, and a difficulty to achieve a coating having a thickness of less than about 10 μm. Further, this method has a problem of very low biological reactivity in that hydroxyapatite coated on the surface of titanium undergoes decomposition in vivo due to a very high crystallinity or is refractory to removal by osteoclasts. Further, this method is known to involve simultaneous formation of calcium phosphates or calcium hydroxides having different phases as by-products (see H.-G. Pfaff, et al., Properties of HA-Coatings in ‘Bioceramics’, vol. 6, P. Ducheyne and D. Christiansen, Eds., pp. 419-424, Butterworth-Heinemann Ltd. (1993)). Generally, bones in the human body undergo a series of processes named as Bone Remodeling where an old bone is removed from the skeleton and a new bone is added. A hydroxyapatite coating film having a high crystallinity does not take part in the remodeling process of bones. Accordingly, hydroxyapatite remains as a coating film for a long period of time in the human body. Even after a functional bone is generated, the coating film exists and decomposes into by-products having different phases, which contributes to peeling of the coating film from the surface, finally resulting in the separation of an implant. To this end, there is a need for the development of low crystalline hydroxyapatite which is capable of taking part in a remodeling process of bones through the in vivo absorption by osteoclasts, thereby overcoming problems of conventional hydroxyapatite coating layers having high crystallinity.
Further, sputtering or ion implantation, apart from high-priced equipment for this purpose, has suffered from various problems such as complex shapes, poor uniformity of the coating layer formed on irregular parts, and detachment of implants due to the peeling-off phenomenon in the human body.
On the other hand, as a wet coating method, there is a method using a calcium phosphate solution or a simulated body fluid. Preparation or coating of various types of calcium phosphates is started from a calcium phosphate ion solution. These calcium phosphate compounds can be prepared by mixing calcium ions and phosphate ions in an aqueous solution under a variety of conditions. In this connection, it is known that the type and form of compounds are greatly affected by ion concentrations, Ca/P ratios and pH conditions (see Ayako Oyane, Kazuo Onuma, Tadashi Kokubo, and Atsuo Ito J. Phys. Chem. B 1999, 103, 8230-8235; J. C. Elliott, In Structure and Chemistry of the Apatites and Other Calcium Orthophosphates, Studies in Inorganic Chemistry 18, Amsterdam: Elsevier, pp 111-190 (1994)). The above-exemplified coating processes involve complicated steps or require a long coating time. Generally, it is difficult for a supersaturated solution of calcium phosphate to maintain a constant concentration, due to spontaneous precipitation (see H. B. Wen, et al., J. Biomed. Mater. Res. 41, 227-236(1998)). Further, a process which is performed under a limited condition of maintaining about 37° C. may take a long period of time, about one month or more, depending on conditions of the surface. In order to solve these problems, there have been developed methods of coating an implant with calcium phosphate by lowering the process temperature and applying a buffer system of phosphate ions to thereby inhibit the precipitation of calcium phosphate crystals in a supersaturated solution. However, these methods also require the use of acids for the manufacture of a calcium ion solution and a phosphate ion solution, and the adjustment of pH (hydrogen ion concentration) by admixture with a base solution at a low temperature for the inhibition of calcium phosphate precipitation. In addition, these methods also do not overcome limitations of a complex and long process time (Korean Patent Application No. 1999-38528 to Kim Hyun-Man, et al., and Korean Patent Application No. 2000-51923 to Kim Se-Won, et al., both assigned to Oscotec Inc.), since it needs for example, purification (by porous filtration or centrifugation) for removing amorphous calcium phosphate which is generated at the beginning of mixing the calcium ion solution and the phosphate ion solution.
Calcium phosphate compounds using a wet method have different equilibrium phases, depending on temperatures and pH values. In particular, at a temperature of 40° C. or lower, calcium phosphate has an equilibrium phase of amorphous (Ca3(PO4)2.nH2O; n=3 to 4.5) or nonstoichiometric hydroxyapatite (Ca10-x(HPO4)x(PO4)6-x(OH)2-x.nH2O; x=0 to 1, n=0 to 2) at a pH of 7 or higher, an equilibrium phase of octacalcium phosphate (OCP, Ca8H2(PO4)6.5H2O) at a pH of 6 to 7, and an equilibrium phase of dicalcium phosphate (DCP, CaHPO4), dicalcium phosphate dihydrous (DCPD, CaHPO4.2H2O) or the like at a pH of 6 or lower. The calcium phosphate coating according to a conventional wet method is based on change of calcium phosphate solubility, taking advantage of the fact that the solubility of calcium phosphate decreases as the reaction temperature increases. Therefore, an initial process should proceed at a low temperature of 2° C. to 5° C., and it is very difficult to obtain a coating film of calcium phosphate as well as a colloidal solution of calcium phosphate without the elevation of temperature. Further, during the process in which the colloidal solution and coating film of calcium phosphate are obtained by elevating reaction temperature, a pH of the solution is generally terminated in the range of 6.0 to 6.5. Even though an accurate equilibrium phase of the calcium phosphate coating film according to the conventional wet method has not been fully understood, it seems to be OCP based on the correlation between the temperature and the pH of the calcium phosphate solution.
As discussed above, conventional wet coating methods utilize differences in the solubility of calcium phosphate in response to changes in temperature, and thus are limited by the need to control temperature and/or pH, the need to use elevated reaction temperature, and the complex procedures required for formation of calcium phosphate coating films. Accordingly, the present disclosure provides solutions and alternatives to the complexity of the procedure exhibited by the conventional wet method.